ON THE COVER
Wein et al. demonstrate that the CXCR6–CXCL16 axis directs the migration of lung-resident memory CD8 T cells into the airways and maintains the airway memory CD8 T cell pool. The cover shows the expression of CXCL16 on epithelial cells lining an airway in a human lung. See https://doi.org/10.1084/jem.20181308.
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Brief Definitive Reports
In the present study, Moeller et al. identify a previously unrecognized pathway through which intestinal epithelial cells expressing the novel chitin-binding receptor FIBCD1 can recognize and control intestinal fungal colonization, limit fungal dysbiosis, and dampen intestinal inflammation.
Corticosteroids inhibit antitumor immune responses of immune checkpoint blockade in a dose- and timing-dependent manner. Memory CD8+ T cells with low TCR affinity are selectively suppressed by corticosteroids, necessitating careful and thoughtful corticosteroid use.
Campbell et al. show that intestinal helminth infection generates mucin-mediated host protection at distal mucosal sites driven by interleukin-13 from innate lymphoid cells. This provides an important innate defense mechanism operating against the multiple helminth challenges encountered at mucosal surfaces.
A homozygous SFTPA1 mutation drives necroptosis of type II alveolar epithelial cells in patients with idiopathic pulmonary fibrosis
We identify a homozygous mutation in SFTPA1 in patients with idiopathic pulmonary fibrosis (IPF). The mutation causes increased necroptosis of type II alveolar epithelial cells through the IRE1α–JNK axis, which highlights the necroptosis pathway as a therapeutic target for IPF.
Tissue-resident lung memory CD8+ TRM cells in the lung interstitium and airways are compartmentally separated from TEM cells, and lung airway TRM cells are primarily maintained by the continuous seeding of cells from the lung interstitium.
Lung TRM cells are present in both the interstitium and airways, but factors regulating their localization to these distinct sites are unknown. This work shows that the CXCR6/CXCL16 axis governs the partitioning of TRM cells to different compartments of the lung and maintains the airway TRM cell pool.
Knipfer et al. identify a critical role for the type 2–related chemokine receptor CCR8 on ILC2 functions during type 2 immune responses. CCR8 supports ILC2 survival by autocrine secretion of the ligand CCL1. The authors demonstrate that CCL1/CCR8 signaling protects against helminth infections.
Lam et al. characterize a novel hematological/autoinflammatory disorder due to a de novo recurrent missense mutation of CDC42. The authors use in silico, in vitro, and in vivo analyses to correlate the molecular mechanisms altering CDC42 function to the observed phenotype.
Concomitant PIK3CD and TNFRSF9 deficiencies cause chronic active Epstein-Barr virus infection of T cells
Identification of biallelic loss-of-function mutations in TNFRSF9 and PIK3CD in a kindred with chronic active Epstein-Barr virus infection of T cells (CAEBV) suggests that CAEBV is the consequence of factors providing growth advantage to EBV-infected T cells combined with defective cell immunity toward EBV-infected cells.
TGF-β signaling controls Foxp3 methylation and T reg cell differentiation by modulating Uhrf1 activity
How DNA methylation–mediated repression is reversed before Foxp3 transcription is unclear. Here, Sun et al. show that the epigenetic regulator Uhrf1, which maintained Foxp3 methylation, is down-regulated by TGF-β signaling and provide novel insight into the epigenetic regulation of Foxp3 during iT reg cell differentiation.
Platelet-activating factor (PAF) can drive pathophysiological inflammation, but the mechanism remains incompletely understood. Here, Deng et al. report that PAF activates the canonical NLRP3 inflammasome independently of its receptor PAFR.
The authors examined a specific RIG-I agonist, SLR14, as an antitumor agent in mice. Intratumoral administration of SLR14 induces robust and long-term antitumor responses against primary, distal, and metastatic tumor as a single agent and improves efficacy of anti-PD1 therapy.
Di Biase et al. show for the first time that creatine acts as a “molecular battery” conserving bioenergy to power CD8 T cell activities; that creatine uptake is critical in supporting antitumor T cell immunity; and that creatine supplementation holds promise for improving cancer immunotherapy.
Primary prostate cancer educates bone stroma through exosomal pyruvate kinase M2 to promote bone metastasis
This study identifies a novel pathway through which PCa selectively metastasizes to bone. PCa cells produce exosomes that transfer pyruvate kinase M2 to BMSCs, which in turn produce CXCL12 that promotes PCa invasion and growth.
Correction: Cytosolic PCNA interacts with p47phox and controls NADPH oxidase NOX2 activation in neutrophils